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Endotoxin‐induced vasodilatation in anaesthetized rat skin involves nitric oxide and prostaglandin synthesis
Author(s) -
Warren J.B.,
Coughlan M.L.,
Williams T.J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14441.x
Subject(s) - chemistry , nitric oxide , endocrinology , vasodilation , nitric oxide synthase , medicine , in vivo , saline , omega n methylarginine , prostaglandin , blood flow , lipopolysaccharide , prostanoid , pharmacology , biology , microbiology and biotechnology
1 The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo . 2 Local skin blood flow changes were measured hourly for 6 h in the shaved dorsal skin with a laser‐Doppler flow probe and compared to changes in control sites which had been injected with 100 μl of phosphate‐buffered saline. By 3 h, skin blood flow increased above basal by 129 ± 27% and 186 ± 29% with 1 and 10 μg of endotoxin respectively. Blood flow remained significantly elevated at 6 h, the corresponding figures being 129 ± 24% and 154 ± 31% ( P < 0.05, n = 6 rats, mean ± s.e.mean). 3 In further experiments, the response to 3 μg of endotoxin was measured at 4 h and treatment with a cyclo‐oxygenase inhibitor, nitric oxide synthase inhibitors or a topical steroid all significantly inhibited this response ( P < 0.05 in each case, n = 6 rats in each group with duplicate sites in each animal). 4 Indomethacin 3 × 10 −9 mol per site injected 3.5 h after injection of endotoxin suppressed the mean 4 h response to endotoxin by 78%; N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) 10 −7 mol per site suppressed the response by 95%; N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA) 10 −7 mol per site suppressed the response by 50%; whereas the d ‐isomer of N G ‐monomethyl‐arginine 10 −7 mol per site had no significant effect. 5 Topical application of the corticosteroid, betamethasone 17‐valerate (1% solution) 18 h before injection of endotoxin inhibited the mean 4 h response to endotoxin by 66% and the 6 h response by 48%. 6 In the same model, the vasodilator response to arachidonic acid was inhibited by both indomethacin and nitric oxide synthase inhibitors ( P < 0.05 in each case). 7 These data suggest that the microcirculatory vasodilator response to endotoxin and arachidonic acid injected locally involves both nitric oxide synthase and cyclo‐oxygenase in this in vivo model.